Crystal structure of a thwarted mismatch glycosylase DNA repair complex

The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release.     

siRNA therapeutics: a clinical reality

Since the revolutionary discovery of RNA interference(RNAi), a remarkable progress has been achieved in understanding and harnessing gene silencing mechanism; especially in small interfering RNA(siRNA) therapeutics. Despite its tremendous potential benefits, major challenges in most siRNA therapeutics remains unchanged—safe, efficient and target oriented delivery of siRNA. Twenty years after the discovery of RNAi, siRNA therapeutics finally charts its way into clinics. As we journey through the decades, we reminisce the history of siRNA discovery and its application in a myriad of disease treatments. Herein,we highlight the breakthroughs in si RNA therapeutics, with special feature on the first FDA approved RNAi therapeutics Onpattro(Patisiran) and the consideration of effective siRNA delivery system focusing on current siRNA nanocarrier in clinical trials. Lastly, we present some challenges and multiple barriers that are yet to be fully overcome in siRNA therapeutics.     

School-age involvement in sport and perceived quality of sport services

Creating an active and healthy lifestyle starts in infancy and adolescence. A number of individual and collective factors affect whether or not sport is taken up and continued, which is an essential element in achieving a healthy lifestyle in adolescence and extending this into adult life. This study sets out to determine the perceived quality of the sport service provided by schools with organised physical activities, and whether the most positively assessed public organisations have a higher percentage of participation than those with a more negative assessment. The study population was 1109 adolescents from 28 towns comprising part of a sport provision system. A self-devised questionnaire with all the necessary properties, validity and reliability was conducted. The results showed that 42% of the adolescents take part in organised physical sport, and give the service provided a positive assessment. It was found that in organisations with a more positive assessment, the town has a higher rate of involvement in sporting activities.     

Visual event-related potentials evoked by using a virtual reality display

This study aimed at investigating whether a virtual reality display (VRD) is an appropriate tool for evoking visual event-related potentials (VEPs). VEPs evoked by VRD stimuli were highly similar in form to VEPs evoked by using a computer monitor, both having two dominant peaks, labeled P100 and N200. Monitor and VRD N200 latencies and amplitudes were highly correlated. However, peak latencies were longer and the peaks were broader when stimuli were presented on the VRD. Besides, VRD P100 amplitude was smaller, and an N75 peak could be seen usually only on monitor VEPs.     

Aloe barbadensis: how a miraculous plant becomes reality

Aloe barbadensis Miller is a plant that is native to North and East Africa and has accompanied man for over 5,000 years. The aloe vera plant has been endowed with digestive, dermatological, culinary and cosmetic virtues. On this basis, aloe provides a range of possibilities for fascinating studies from several points of view, including the analysis of chemical composition, the biochemistry involved in various activities and its application in pharmacology, as well as from horticultural and economic standpoints. The use of aloe vera as a medicinal plant is mentioned in numerous ancient texts such as the Bible. This multitude of medicinal uses has been described and discussed for centuries, thus transforming this miracle plant into reality. A summary of the historical uses, chemical composition and biological activities of this species is presented in this review. The latest clinical studies involved in vivo and in vitro assays conducted with aloe vera gel or its metabolites and the results of these studies are reviewed.     

The reality of a self-occluding pump head: Case report

A malfunction of an oxygenator pumphead during aortocoronary bypass surgery is described. Corrections were made and the operation proceeded without further incident. Although this malfunction is extremely rare, it is reviewed in detail to alert perfusionists to the possibility of such an occurrence.     

Zooplankton nutrition: recent progress and a reality check

Evidence suggests that marine and freshwater zooplankton generally experience food levels above subsistence values in terms of carbon. However, the quality of this food may be poor due to an insufficiency of other essential nutrients. In this review, we examine recent progress in three main areas of food quality research: (1) elemental (especially P) limitation, (2) digestion resistance, and (3) biochemical (especially fatty acids) limitation. We evaluate laboratory and field evidence in each of these areas, look at new evidence about the life history implications of the elemental limitation hypothesis, and suggest future avenues for research. From a rather large number of seemingly heterogeneous studies, a single consistent picture of food quality emerges: both P and essential fatty acids are predicted to be important dietary factors, but at different places and times. Nevertheless, despite an abundance of valuable laboratory studies, our knowledge of food quality limitation in the field is still poor.     

Locomotion in elongate fishes: A contact sport

Despite the physical differences between water and air, a number of fish lineages are known to make terrestrial excursions on land. Many of these fishes exhibit an elongate body plan. Elongation of the body can occur in several ways, the most common of which is increasing the number of vertebrae in one or both regions of the axial skeleton – precaudal and/or caudal. Elongate species are often found in three-dimensionally complex habitats. It has been hypothesized that elongate fishes use this structure to their locomotor advantage. In this study, we consider how elongation and differences in vertebral regionalization correspond with the use of wooden pegs, which are provided as analogs to vertically oriented substrate, structures that protrude above the ground. We compare aquatic and terrestrial locomotor behaviors of Polypterus senegalus, Erpetoichthys calabaricus, and Gymnallabes typus as they move through a peg array. When considering axial elongation we find that the highly elongate species, E. calabaricus and G. typus, contact more pegs but on average move slower in both environments than P. senegalus. When considering axial regionalization, we find that the precaudally elongate species, P. senegalus and E. calabaricus, differ in the patterns of peg contact between the two environments whereas the caudally elongate species, G. typus, exhibits similar peg contact between the two environments. Our study highlights the importance of incorporating body shape and vertebral regionalization to understand how elongate fishes move in water and on land.